BMS-986012 in Relapsed/Refractory SCLC

Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1/2 Multicenter Study of BMS-986012 in Subjects With Relapsed/Refractory Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02247349
• Other study ID #: CA001-030
• Secondary ID: 2014-002372-89
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 14, 2014
• Est. completion date: December 22, 2022

Study information

• Verified date: February 2024
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety, tolerability, pharmacokinetics, immunogenicity, antitumor activity and pharmacodynamics of BMS-986012 alone and in combination with nivolumab in patients with relapsed/refractory SCLC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: December 22, 2022
• Est. primary completion date: December 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Histological or cytological confirmed small cell lung cancer (SCLC)

• Performance Status 0-1

• Adequate organ function

• Measurable disease

Exclusion Criteria:

• Known or suspected brain metastasis

• Small cell cancer not lung in origin

• Significant or acute medical illness

• Uncontrolled or significant cardiac disease

• Infection

• = Grade 2 peripheral neuropathy

• Concomitant malignancies

• HIV related disease or known or suspected HIV+

• Hepatitis B or C infection

• ECG abnormalities as defined by the protocol

• Allergies or hypersensitivities to monoclonal antibodies, BMS-986012 or related compounds, including fucosyl-GM1 vaccine and Nivolumab

Other protocol defined inclusion/exclusion criteria could apply

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Biological:
• BMS-986012 (anti-fucosyl-GM1)

• Nivolumab

Locations

Country	Name	City	State
Australia	Local Institution - 0011	Brisbane	Queensland
Australia	Local Institution - 0002	Clayton	Victoria
Australia	Local Institution - 0020	St. Leonards	New South Wales
Belgium	Local Institution - 0015	Gent
Belgium	Local Institution - 0012	Liege
Canada	Local Institution - 0003	Edmonton	Alberta
Canada	Local Institution - 0017	Halifax	Nova Scotia
Canada	Local Institution - 0019	Hamilton	Ontario
Canada	Local Institution - 0010	London	Ontario
Canada	Local Institution - 0007	Toronto	Ontario
Korea, Republic of	Local Institution - 0008	Seoul
Netherlands	Local Institution - 0013	Nijmegen
Puerto Rico	Local Institution - 0009	San Juan
United States	Local Institution - 0001	Durham	North Carolina
United States	Local Institution - 0004	New York	New York
United States	Local Institution - 0021	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Korea, Republic of,  Netherlands,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs)	Number of participants with any grade adverse events (AEs). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From first dose to 100 days post last dose (Up to 64 months)
Primary	Number of Participants With Serious Adverse Events (SAEs)	Number of participants with any grade serious adverse events (SAEs). A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From first dose to 100 days post last dose (Up to 64 months)
Primary	Number of Participants With Adverse Events (AEs) Leading to Discontinuation	Number of participants with any grade adverse events (AEs) leading to discontinuation. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From first dose to 100 days post last dose (Up to 64 months)
Primary	Number of Participants Who Died	Number of participants who died due to any cause.	From first dose to 100 days post last dose (Up to 64 months)
Primary	Number of Participants With Abnormal Hepatic Test	Number of participants with laboratory abnormalities in specific hepatic tests. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: ALT or AST > 5xULN, > 3xULN, and > 2xULN; Any of ALT, AST, Total Bilirubin or ALP > 8xULN; Total bilirubin > 3xULN; ALT = Alanine Aminotransferase; AST = Aspartate Aminotransferase; ULN = Upper Limit of Normal	From first dose to 100 days post last dose (Up to 64 months)
Secondary	BMS-986012 Maximum Observed Serum Concentration (Cmax)	BMS-986012 maximum observed serum concentration (Cmax).	Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
Secondary	BMS-986012 Time of Maximum Observed Serum Concentration (Tmax)	BMS-986012 time of maximum observed serum concentration (Tmax).	Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
Secondary	BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T))	BMS-986012 area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC (0-T)).	Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
Secondary	BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU)	BMS-986012 area under the serum concentration-time curve in one dosing interval AUC (TAU).	Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
Secondary	BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau)	BMS-986012 observed serum concentration at the end of a dosing interval (Ctau).	Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
Secondary	BMS-986012 Total Body Clearance (CLT)	BMS-986012 total body clearance (CLT).	Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
Secondary	BMS-986012 Trough Observed Serum Concentration (Ctrough)	BMS-986012 trough observed serum concentration (Ctrough).	Cycle 2 day 1, cycle 3 day 1, cycle 4 day 1, cycle 7 day 1, cycle 11 day 1. cycle 15 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
Secondary	BMS-986012 Average Concentration Over a Dosing Interval (Css-avg)	BMS-986012 Average concentration over a dosing interval ([AUC(TAU)/tau] (Css-avg).	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
Secondary	BMS-986012 Accumulation Index (AI_AUC)	BMS-986012 accumulation index. Ratio of an exposure measure at steady state to that after the first dose.	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
Secondary	BMS-986012 Cmax Accumulation Index (AI_Cmax)	BMS-986012 Cmax accumulation index (AI_Cmax). Ratio of an exposure measure at steady state to that after the first dose.	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
Secondary	BMS-986012 Ctau Accumulation Index (AI_Ctau)	BMS-986012 Ctau accumulation index (AI_Ctau). Ratio of an exposure measure at steady state to that after the first dose.	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
Secondary	BMS-986012 Effective Elimination (T-HALFeff)	BMS-986012 effective elimination (T-HALFeff) that explains the degree of accumulation observed for a specific exposure measure.	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
Secondary	Best Overall Response (BOR)	BOR defined as the best response designation over the study as a whole. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = At least a 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm	From first dose to the last tumor assessment prior to subsequent therapy (Up to 97 months)
Secondary	Objective Response Rate (ORR)	ORR is defined as the percent of participants whose BOR is either CR or PR. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm	From first dose date to the date of first documented disease progression (Up to 97 months)
Secondary	Duration of Response (DoR)	DoR is defined as the time from first response (CR or PR) to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who remain alive and have not progressed will be censored on the date of their last tumor assessment.; Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR )= At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm; Median DOR will only be evaluated provided there are enough responding participants to warrant inclusion.	From the date of first dose to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 97 months)
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from the date of first dose of study medication to the date of the first objective documentation of tumor progression or death due to any cause, if death occurred within 100 days after last BMS-986012 dose.; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm	From first dose to the date of first documented disease progression or death due to any cause, if death occurred within 100 days after last BMS-986012 dose (Up to 97 months)
Secondary	Progression Free Survival Rate (PFSR)	PFSR is defined as the percent of participants who remain progression free and surviving at "t" weeks (t= 12, 24, 36, 48, 60, 72).; Progressive Disease (PD)=At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm	Weeks 12, 24, 36, 48, 60, 72
Secondary	Number of Participants With Anti-BMS-986012 Antibodies (ADA)	Number of participants with anti-BMS-986012 antibodies (ADA) with status as baseline ADA positive, ADA positive and ADA negative. Baseline ADA positive participant is a participant with baseline ADA positive sample (Day 1 predose). ADA-positive participant is a participant with at least one ADA positive sample relative to baseline at any time after initiation of treatment during the defined observation time period. ADA negative participant is a participant with no ADA positive sample after the initiation of treatment.	From first dose to 100 days following the last BMS-986012 dose (Up to 64 months)

External Links

•   BMS Clinical Trial Information
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